12-113159109-C-T

Position:

chr12-113159109-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024072.4(DDX54):c.2414G>A(p.Gly805Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000487 in 1,438,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

DDX54
NM_024072.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Variant links:

Genes affected

DDX54 (HGNC:20084): (DEAD-box helicase 54) This gene encodes a member of the DEAD box protein family. DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The nucleolar protein encoded by this gene interacts in a hormone-dependent manner with nuclear receptors, and represses their transcriptional activity. Alternative splice variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DDX54 links:

CFAP73 (HGNC:37100): (cilia and flagella associated protein 73) Predicted to enable dynein complex binding activity. Predicted to be involved in cilium movement and inner dynein arm assembly. Predicted to be located in axonemal outer doublet and motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

CFAP73 links:

MIR7106 (HGNC:50085): (microRNA 7106) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR7106 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11816046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DDX54	NM_024072.4 linkuse as main transcript	c.2414G>A	p.Gly805Asp	missense_variant, splice_region_variant	20/20	ENST00000306014.10
CFAP73	NM_001144872.3 linkuse as main transcript	c.*420C>T		3_prime_UTR_variant	8/8	ENST00000335621.11
DDX54	NM_001111322.2 linkuse as main transcript	c.2417G>A	p.Gly806Asp	missense_variant	20/20
MIR7106	NR_106956.1 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX54	ENST00000306014.10 linkuse as main transcript	c.2414G>A	p.Gly805Asp	missense_variant, splice_region_variant	20/20	1	NM_024072.4	A1	Q8TDD1-1
CFAP73	ENST00000335621.11 linkuse as main transcript	c.*420C>T		3_prime_UTR_variant	8/8	5	NM_001144872.3	P1
MIR7106	ENST00000612419.1 linkuse as main transcript			downstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000947

AC:

AN:

211100

Hom.:

AF XY:

0.00

AC XY:

AN XY:

115510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000217

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000487

AC:

AN:

1438546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000635

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000567

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.2417G>A (p.G806D) alteration is located in exon 20 (coding exon 20) of the DDX54 gene. This alteration results from a G to A substitution at nucleotide position 2417, causing the glycine (G) at amino acid position 806 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.76

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.063

Sift

Benign

0.18

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.67

P;P

Vest4

0.20

MutPred

0.23

.;Gain of catalytic residue at P809 (P = 0.0196);

MVP

0.19

MPC

0.42

ClinPred

0.15

GERP RS

4.2

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

Varity_R

0.041

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over